1998 Curt P. Richter AwardPregnancy, the postpartum, and steroid hormones: effects on cognition and mood
Introduction
Cognitive and mood changes during pregnancy and in the postpartum period are frequently self-reported and have been documented empirically. Mood, as it relates to pregnancy, has been addressed primarily in relation to postnatal depression. However, available estimates of negative affective symptomatology during pregnancy suggest a sizable proportion of women are affected (Nott et al., 1976, O’Hara et al., 1984, O’Hara, 1986). Mood changes in the postnatal period include mild forms of dysphoria, typically referred to as the blues (Harris, 1980, Pritchard and Harris, 1996), and anxiety and tearfulness (Kennerly and Gath, 1986). Mild to moderate depression is ≈3× higher in the month following delivery than in non-gestational controls (O’Hara et al., 1990).
While negative affective state has been investigated in relation to a number of sociodemographic variables, postnatal depressed mood has been related to the hormonal changes of the perinatal period. Nott et al. (1976) report a correlational trend for greater antenatal irritability with higher estrogen levels, as well as a greater likelihood for subjects with larger progesterone (P) declines to rate themselves as depressed postnatally. O’Hara (1986) also examined P and mood from the second trimester of pregnancy to the 9th postpartum week but failed to find a similar correlation. However, estrogen withdrawal was identified as a possible cause of postpartum blues. A prospective study of primiparous women, which assessed mood and concentrations of P and cortisol antenatally and in the month following parturition, found that women with maternity blues had significantly higher antenatal P concentrations and lower postnatal concentrations than women without blues (Harris et al., 1994). In contrast, Heidrich et al. (1994) reports no significant difference in estradiol (E2) or P levels between women with and without postpartum blues.
Estrogen levels may be associated with changes in mood in non-pregnant women. The use of ERT is associated with less depression in the post-menopause (Sherwin and Gelfand, 1985, Ditkoff et al., 1991). Hormonal fluctuations across the menstrual cycle have been inconsistently associated with changes in mood (Halbreich et al., 1986, Phillips and Sherwin, 1992b, Redei and Freeman, 1995, Fink et al., 1996).
Fewer studies have analyzed cognitive changes during and after pregnancy. Sharp et al. (1993) found deficits in the recall of word lists in both primigravid and multigravid pregnant women when compared with non-pregnant women. This deficit was greater for incidental recall than when the women were explicitly instructed to remember items. A similar pattern was found for pregnant women in all trimesters of pregnancy. Eidelman et al. (1993) found that women in the 3rd month of a high risk pregnancy performed worse than nonpregnant controls on the ability to recall a short passage of prose, but not on a visual memory task. In a separate group of women with normal pregnancies, deficits in both passage recall and visual memory were reported during the 1st postpartum day but not during days two and three. Silber et al. (1990), testing women in the 36th week of pregnancy, within 3 days after delivery, and at 3, 6 and 12 months postpartum, found no differences between pregnant women and controls during pregnancy, at the immediate postpartum or at the 3 month testing. However, the women who had been pregnant showed significant increases in performance on word list learning and reaction time at the 6 and 12 month testings, when compared with the controls. The authors interpret this as indicative of a peripartal cognitive impairment. In a longitudinal study, Keenan et al. (1997), find explicit memory deficits, using paragraph recall, only in the third trimester, when pregnant women are compared with controls. Subjective reports of cognitive dysfunction during pregnancy have been noted. Poser et al. (1986) found symptoms such as forgetfulness, disorientation, confusion, and reading difficulties to be common among pregnant professional women. Subjective memory complaints during pregnancy have also been associated with impairments in implicit memory (Brindle et al., 1991). None of the studies on cognitive functioning have simultaneously evaluated mood, which is essential to determine if cognitive changes are reflective of changes in mood.
The mechanism for any cognitive changes associated with pregnancy remains to be determined. Silber et al. (1990) found no consistent associations between cognitive changes and changes in oxytocin levels. In studies not involving pregnancy, there is compelling support for an effect of steroid hormones on both cognitive and mood functioning. Among women, fluctuations in circulating estrogens, from either endogenous or exogenous sources, are associated with specific cognitive profiles. This has been most widely reported for administration of estrogen replacement to women after either surgical (Sherwin, 1988, Phillips and Sherwin, 1992a) or natural menopause (Kampen and Sherwin, 1994, Robinson et al., 1994). Studies also suggest that the estrogen deficiency that results with the use of gonadotropin-releasing-hormone (GnRH) agonists is associated with decreased memory (Kortepeter et al., 1992, Newton et al., 1996), an effect that is reversed by add-back estrogen therapy (Sherwin and Tulandi, 1996). Endogenous fluctuations in estrogen associated with the menstrual cycle have also been associated with cognitive changes such that specific cognitive skills are elevated at times during the cycle when estrogen levels are high (Hampson and Kimura, 1988, Hampson, 1990).
Other hormones have been associated with cognitive and mood status including P (Freeman et al., 1993, Baker et al., 1995), testosterone (T) (Janowsky et al., 1994, Sands and Studd, 1995), dehydroepiandrosterone (DHEA) (Morales et al., 1994, Wolkowitz et al., 1997), and cortisol (Carroll et al., 1981, Lupien et al., 1994). These hormones also change dramatically during pregnancy and with parturition.
In an effort to better understand both the cognitive and mood effects of pregnancy and the postpartum, we evaluated a group of women during the last month of pregnancy and again within 2–6 weeks after delivery. These times were chosen to allow for a determination of the effects of late pregnancy, when hormones are elevated, in comparison with performance in the postpartum, after the initial trauma of labor has subsided, while steroid hormones are still greatly reduced. We utilized a comprehensive battery of neuropsychological tests that have widely used norms available. Tests of mood are included to allow for evaluation of mood during and after pregnancy and to be able to determine if any cognitive changes are independent of mood. A range of steroid hormones, known to have effects on cognition and mood, were evaluated in an attempt to elucidate the mechanism underlying any effects of pregnancy and the postpartum on cognition or mood.
Section snippets
Subjects
Participants were recruited through private practice offices of Los Angeles area gynecologists and through birthing classes conducted at a major Los Angeles hospital. All subjects were primary English-speakers and had uncomplicated pregnancies. Twenty-five subjects were enrolled into the study and 19 completed the neuropsychological tests on both occasions and are included in current analyses. The average age of the subjects was 33.1 years (±4.7) and average education was 16.0 years (±1.3).
Pregnancy and cognition
Descriptive and statistical information for all cognitive tests is provided in Table 2. Subjects showed no change in general intelligence level during and after pregnancy, performing slightly above the mean at both testing occasions, on the TONI. On the CVLT, subjects performed significantly worse when pregnant on the number of items recalled after the fifth trial (F=13.23, p=.002). Subjects also showed a significantly lower learning slope across the five learning trials when pregnant (F=5.13, p
Discussion
These findings confirm previous reports of peripartal cognitive deficits (Poser et al., 1986, Silber et al., 1990, Brindle et al., 1991, Eidelman et al., 1993, Sharp et al., 1993, Keenan et al., 1997). Specifically, cognitive performance was worse, in certain domains, during pregnancy than relatively shortly after delivery, although performance continued below expected normative values on aspects of verbal memory. Subjects did not report greater mood disturbances after delivery, rather there
Acknowledgements
The impetus for this study came from discussions with Caleb E. Finch, Ph.D., and his seminal work on reproduction and senescence. Portions of this study were presented at the International Neuropsychological Society Meeting, Orlando FL, February, 1997 and at the Society for Gynecologic Investigations, San Diego CA, March, 1997.
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